Genomic analysis of “microphenotypes” in epilepsy
Large international consortia examining the genomic architecture of the epilepsies focus on large diagnostic subgroupings such as “all focal epilepsy” and “all genetic generalized epilepsy”. In addition, phenotypic data are generally entered into these large discovery databases in a unidirectional m...
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Veröffentlicht in: | American journal of medical genetics. Part A 2022-01, Vol.188 (1), p.138-146 |
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creator | Stanley, Kate Hostyk, Joseph Tran, Linh Amengual‐Gual, Marta Dugan, Patricia Clark, Justice Choi, Hyunmi Tchapyjnikov, Dmitry Perucca, Piero Fernandes, Cecilia Andrade, Danielle Devinsky, Orrin Cavalleri, Gianpiero L. Depondt, Chantal Sen, Arjune O'Brien, Terence Heinzen, Erin Loddenkemper, Tobias Goldstein, David B. Mikati, Mohamed A. Delanty, Norman |
description | Large international consortia examining the genomic architecture of the epilepsies focus on large diagnostic subgroupings such as “all focal epilepsy” and “all genetic generalized epilepsy”. In addition, phenotypic data are generally entered into these large discovery databases in a unidirectional manner at one point in time only. However, there are many smaller phenotypic subgroupings in epilepsy, many of which may have unique genomic risk factors. Such a subgrouping or “microphenotype” may be defined as an uncommon or rare phenotype that is well recognized by epileptologists and the epilepsy community, and which may or may not be formally recognized within the International League Against Epilepsy classification system. Here we examine the genetic structure of a number of such microphenotypes and report in particular on two interesting clinical phenotypes, Jeavons syndrome and pediatric status epilepticus. Although no single gene reached exome‐wide statistical significance to be associated with any of the diagnostic categories, we observe enrichment of rare damaging variants in established epilepsy genes among Landau–Kleffner patients (GRIN2A) and pediatric status epilepticus patients (MECP2, SCN1A, SCN2A, SCN8A). |
doi_str_mv | 10.1002/ajmg.a.62505 |
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In addition, phenotypic data are generally entered into these large discovery databases in a unidirectional manner at one point in time only. However, there are many smaller phenotypic subgroupings in epilepsy, many of which may have unique genomic risk factors. Such a subgrouping or “microphenotype” may be defined as an uncommon or rare phenotype that is well recognized by epileptologists and the epilepsy community, and which may or may not be formally recognized within the International League Against Epilepsy classification system. Here we examine the genetic structure of a number of such microphenotypes and report in particular on two interesting clinical phenotypes, Jeavons syndrome and pediatric status epilepticus. Although no single gene reached exome‐wide statistical significance to be associated with any of the diagnostic categories, we observe enrichment of rare damaging variants in established epilepsy genes among Landau–Kleffner patients (GRIN2A) and pediatric status epilepticus patients (MECP2, SCN1A, SCN2A, SCN8A).</description><identifier>ISSN: 1552-4825</identifier><identifier>EISSN: 1552-4833</identifier><identifier>DOI: 10.1002/ajmg.a.62505</identifier><identifier>PMID: 34569149</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Child ; Epilepsy ; Epilepsy - diagnosis ; Epilepsy - genetics ; Epilepsy, Generalized - diagnosis ; Epilepsy, Generalized - genetics ; Exome ; Genetic structure ; Genomic analysis ; Genomics ; Humans ; Jeavons syndrome ; MeCP2 protein ; Methyl-CpG binding protein ; microphenotype ; Patients ; pediatric status epilepticus ; Pediatrics ; Phenotype ; Phenotypes ; Risk factors ; Sodium channels (voltage-gated)</subject><ispartof>American journal of medical genetics. 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subjects | Child Epilepsy Epilepsy - diagnosis Epilepsy - genetics Epilepsy, Generalized - diagnosis Epilepsy, Generalized - genetics Exome Genetic structure Genomic analysis Genomics Humans Jeavons syndrome MeCP2 protein Methyl-CpG binding protein microphenotype Patients pediatric status epilepticus Pediatrics Phenotype Phenotypes Risk factors Sodium channels (voltage-gated) |
title | Genomic analysis of “microphenotypes” in epilepsy |
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